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血清碱性磷酸酶与2型糖尿病合并非酒精性脂肪肝病的相关性分析
DOI: 10.3969/j.issn.1001-5256.2023.01.013
伦理学声明：本研究于2018年12月17日经由江苏大学附属医院伦理委员会审批，批号：SWYXLL20181217-1。
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明：钱方方、戴梅清负责课题设计，资料分析，论文撰写；赵丽、邓霞、杨玲、贾珏、王济芳、王东参与收集数据，修改论文；袁国跃负责拟定写作思路，指导撰写文章及最后定稿。
Association between serum alkaline phosphatase and type 2 diabetes mellitus with nonalcoholic fatty liver disease
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摘要:
目的 探讨血清碱性磷酸酶(ALP)与2型糖尿病(T2DM)合并非酒精性脂肪性肝病(NAFLD) 的相关性。 方法 选取2016年7月—2018年12月于江苏大学附属医院内分泌科住院的599例T2DM患者为研究对象。根据是否合并NAFLD分为NAFLD组(286例)和非NAFLD组(313例)，根据腹部超声检查结果将NAFLD患者分为轻度(111例)、中度(105例)、重度(70例)三组，比较各组间一般临床资料的差异。正态分布的计量资料两组间比较采用独立样本t检验，三组间比较采用方差分析；非正态分布计量资料两组间比较采用Mann-Whitney U检验；三组间比较使用Kruskal-Wallis H秩和检验，计数资料组间比较采用χ2检验。采用Pearson相关分析法和Spearman相关分析法分析ALP与临床指标的相关性。Logistic回归分析NAFLD的影响因素。 结果 NAFLD组高血压病史所占比例、收缩压、舒张压、BMI、腰围(WC)、空腹胰岛素(FIns)、空腹C肽、血尿酸、低密度脂蛋白胆固醇、TG、TC、稳态模型评估胰岛素抵抗指数(HOMA-IR)、ALT、AST、GGT、ALP均高于非NAFLD组(χ2= 7.864、t=-2.226、t=-3.800、t=-11.842、t=-9.150、Z=-6.173、t=-5.419、t=-4.957、t=-2.702、Z=-9.376、t=-3.016、Z=-5.794、Z=-6.737、Z=-4.389、Z=-7.764、t=-2.833，P值均＜0.05)。NAFLD组年龄、高密度脂蛋白胆固醇均低于非NAFLD组(t=2.184、Z=-5.273，P值均＜0.05)。NAFLD脂肪肝的严重程度(轻、中、重)与年龄(rs=0.140)、BMI(rs=0.239)、WC(rs=0.222)、FIns(rs=0.191)、HOMA-IR(rs=0.218)、ALT(rs=0.188)、AST(rs=0.279)、GGT(rs=0.202)、ALP(rs=0.361)呈正相关(P值均＜0.05)。在T2DM合并NAFLD患者中，ALP与糖化血红蛋白(r=0.149)、空腹血糖(r=0.146)、HOMA-IR(rs=0.132)、TC(r=0.151)、ALT(rs=0.210)、AST(rs=0.192)、GGT(rs=0.297)呈正相关(P值均＜0.05)。Logistic回归分析显示，ALP是T2DM患者发生NAFLD的影响因素(OR=1.013，95%CI：1.004~1.023，P＜0.05)。 结论 血清ALP升高是T2DM合并NFALD的危险因素，且与高血糖、胰岛素抵抗、高血脂密切相关，可能在T2DM和NFALD疾病的发生发展中起一定作用。 Abstract:Objective To investigate the association between serum alkaline phosphatase (ALP) and type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). Methods A total of 599 patients with T2DM who were hospitalized in Department of Endocrinology, Affiliated Hospital of Jiangsu University, from July 2016 to December 2018 were enrolled as subjects. According to the presence or absence of NAFLD, the patients were divided into NAFLD group with 286 patients and non-NAFLD group with 313 patients, and according to the results of abdominal ultrasound, the patients with NAFLD were divided into mild group with 111 patients, moderate group with 105 patients, and severe group with 70 patients. General clinical data were compared between groups. The independent samples t- test was used for comparison of normally distributed continuous data between two groups, and an analysis of variance was used for comparison between three groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between three groups; the chi-square test was used for comparison of categorical data between groups. Pearson correlation analysis and Spearman correlation analysis were used to investigate the correlation between ALP and clinical indices, and a logistic regression analysis was used to investigate the influencing factors for NAFLD. Results Compared with the non-NAFLD group, the NAFLD group had significantly higher proportion of patients with history of hypertension (χ2=7.864, P < 0.05), systolic blood pressure (t=-2.226, P < 0.05), diastolic blood pressure (t=-3.800, P < 0.05), body mass index (BMI) (t=-11.842, P < 0.05), waist circumference (WC) (t=-9.150, P < 0.05), fasting insulin (FINS) (Z=-6.173, P < 0.05), fasting C-peptide (t=-5.419, P < 0.05), serum uric acid (t=-4.957, P < 0.05), low-density lipoprotein cholesterol (t=-2.702, P < 0.05), triglyceride (Z=-9.376, P < 0.05), total cholesterol (TC) (t=-3.016, P < 0.05), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (Z=-5.794, P < 0.05), alanine aminotransferase (ALT) (Z=-6.737, P < 0.05), aspartate aminotransferase (AST) (Z=-4.389, P < 0.05), gamma-glutamyl transpeptidase (GGT) (Z=-7.764, P < 0.05), and ALP (t=-2.833, P < 0.05), as well as significantly lower age (t=2.184, P < 0.05) and high-density lipoprotein cholesterol (Z=-5.273, P < 0.05). The severity of NAFLD (mild, moderate or severe) was positively correlated with age (rs=0.140, P < 0.05), BMI (rs=0.239, P < 0.05), WC (rs=0.222, P < 0.05), FINS (rs=0.191, P < 0.05), HOMA-IR (rs=0.218, P < 0.05), ALT (rs=0.188, P < 0.05), AST (rs=0.279, P < 0.05), GGT (rs=0.202, P < 0.05), and ALP (rs=0.361, P < 0.05). In the patients with T2DM and NAFLD, ALP was positively correlated with HbAlc (r=0.149, P < 0.05), fasting plasma glucose (r=0.146, P < 0.05), HOMA-IR (rs=0.132, P < 0.05), TC (r=0.151, P < 0.05), ALT (rs=0.210, P < 0.05), AST (rs=0.192, P < 0.05), and GGT (rs=0.297, P < 0.05). The logistic regression analysis showed that ALP was an influencing factor for NAFLD in patients with T2DM (odds ratio=1.013, 95% confidence interval: 1.004-1.023, P < 0.05). Conclusion Elevated serum ALP is a risk factor for T2DM with NAFLD and is closely associated with hyperglycemia, insulin resistance, and hyperlipemia, and ALP may play a role in the development and progression of T2DM and NAFLD. -
表 1 两组一般资料及生化指标比较
Table 1. Comparison of general data between groups
项目 non-NAFLD组(n=313) NAFLD组(n=286) 统计值 P值 男性[例(%)] 179(57.2) 141(49.3) χ2= 3.737 0.053 年龄(岁) 64.28±11.15 62.27±11.38 t=2.184 0.029 病程(月) 120(36~192) 120(36~159) Z=-1.365 0.172 BMI(kg/m2) 23.51±2.99 26.49±3.18 t=-11.842 ＜0.001 吸烟史[例(%)] 67(21.4) 60(21.0) χ2=0.016 0.898 高血压病史[例(%)] 174(55.6) 191(66.8) χ2=7.864 0.005 SBP(mmHg) 133.63±15.27 136.44±15.58 t=-2.226 0.026 DBP(mmHg) 78.62±8.77 81.47±9.58 t=-3.800 ＜0.001 WC(cm) 87.46±9.88 94.54±8.98 t=-9.150 ＜0.001 HbA1c(%) 8.89±2.13 8.93±1.73 t=-0.279 0.781 FPG(mmol/L) 9.69±3.71 9.50±3.12 t=0.684 0.495 FIns(μIU/L) 6.25(3.62~11.14) 10.05(5.41~16.72) Z=-6.173 ＜0.001 FC-P(μg/L) 1.74±0.96 2.18±1.04 t=-5.419 ＜0.001 SUA(μmol/L) 269.37±84.92 305.03±91.13 t=-4.957 ＜0.001 LDL-C(mmol/L) 2.54±0.86 2.72±0.75 t=-2.702 0.007 HDL-C(mmol/L) 1.09(0.88~1.34) 0.95(0.81~1.14) Z=-5.273 ＜0.001 TG(mmol/L) 1.28(0.96~1.79) 1.86(1.43~2.69) Z=-9.376 ＜0.001 TC(mmol/L) 4.61±1.10 4.86±0.98 t=-3.016 0.003 HOMA-IR 2.77(1.41~4.44) 3.92(2.19~6.71) Z=-5.794 ＜0.001 ALT(U/L) 14.80(11.05~21.90) 20.20(14.68~30.40) Z=-6.737 ＜0.001 AST(U/L) 14.70(11.35~17.95) 16.90(12.38~23.33) Z=-4.389 ＜0.001 GGT(U/L) 19.00(14.30~28.00) 27.60(20.00~43.55) Z=-7.764 ＜0.001 ALP(U/L) 69.73±19.94 74.71±23.03 t=-2.833 0.005 
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表 2 轻中重度NAFLD患者临床资料比较
Table 2. Comparison of general data among groups in patients with NAFLD
项目 轻度NAFLD组(n=111) 中度NAFLD组(n=105) 重度NAFLD组(n=70) 统计值 P值 男性[例(%)] 58(52.3) 56(53.3) 27(38.6) χ2=4.294 0.117 年龄(岁) 60.5±10.6 63.0±12.0 64.1±11.4 F=2.538 0.081 病程(月) 120(36~168) 108(29~144) 120(33~156) χ2=0.442 0.802 BMI(kg/m2) 25.48±2.59 26.88±2.991) 27.52±3.831) F=10.731 ＜0.001 SBP(mmHg) 136.16±15.64 134.51±14.55 139.76±16.66 F=2.429 0.090 DBP(mmHg) 81.10±9.33 81.57±9.68 81.91±9.92 F=0.163 0.849 WC(cm) 92.17±7.37 95.33±8.381) 97.12±11.141) F=7.502 0.001 HbA1c(%) 8.79±1.72 8.90±1.67 9.22±1.85 F=1.388 0.251 FPG(mmol/L) 9.35±3.04 9.28±3.12 10.06±3.21 F=1.551 0.214 FIns(μIU/L) 7.38(4.61~14.94) 10.25(5.69~16.22) 11.65(7.53~19.62)1) χ2=10.512 0.005 FC-P(μg/L) 2.12±1.07 2.19±1.00 2.28±1.05 F=0.524 0.593 SUA(μmol/L) 293.99±82.32 321.08±88.00 298.46±105.81 F=2.654 0.072 LDL-C(mmol/L) 2.76±0.73 2.66±0.77 2.76±0.77 F=0.603 0.548 HDL-C(mmol/L) 0.95(0.82~1.14) 0.93(0.80~1.11) 0.99(0.82~1.21) χ2=1.749 0.417 TG(mmol/L) 1.84(1.37~2.87) 1.77(1.47~2.59) 1.92(1.45~3.16) χ2=0.679 0.712 TC(mmol/L) 4.83±0.96 4.74±0.91 5.10±1.08 F=2.956 0.054 HOMA-IR 3.32(1.83~5.55) 3.90(2.34~6.51) 5.47(2.96~9.53)1) χ2=14.183 0.001 ALT(U/L) 18.00(13.60~27.60) 22.00(15.10~31.30) 23.95(16.00~42.23)1) χ2=10.453 0.005 AST(U/L) 14.00(11.50~18.40) 18.40(13.00~25.30)1) 20.05(14.25~27.08)1) χ2=22.423 ＜0.001 GGT(U/L) 23.00(17.00~38.80) 27.90(21.05~39.50) 34.50(21.65~55.43)1) χ2=11.791 0.003 ALP(U/L) 65.72±16.63 73.71±20.941) 90.44±26.581)2) F=29.920 ＜0.001 注：与轻度NAFLD组比较，1)P＜0.01；与中度NAFLD组比较，2)P＜0.01。
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表 3 NAFLD患者ALP与临床各指标的相关性分析
Table 3. Correlation analysis between ALP and clinical indicators in patients with NAFLD
项目 r或rs值 P值 HbA1c 0.149 0.012 FPG 0.146 0.014 HOMA-IR 0.132 0.025 TC 0.151 0.011 ALT 0.210 ＜0.001 AST 0.192 0.001 GGT 0.297 ＜0.001
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表 4 Logistic回归分析NAFLD的影响因素
Table 4. Logistic regression analysis of the influencing factors for NAFLD
因素 β值 SE Wald OR 95%CI P值 年龄 -0.030 0.010 8.527 0.971 0.951~0.990 0.003 BMI 0.298 0.037 63.596 1.347 1.252~1.450 ＜0.001 FC-P 0.267 0.111 5.807 1.307 1.051~1.624 0.016 LDL-C 1.332 0.470 8.023 3.787 1.507~9.516 0.005 TG 0.685 0.167 16.803 1.984 1.430~2.752 ＜0.001 ALP 0.013 0.005 7.444 1.013 1.004~1.023 0.006
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